title: Regulation of toxinogenesis in Corynebacterium diphtheriae. I. Mutations in bacteriophage beta that alter the effects of iron on toxin production.
abstract: Diphtherial toxin is produced in maximal yields by Corynebacterium diphtheriae (C7(beta tox+) only when iron is present in growth-limiting amounts. Toxin production is markedly decreased under high-iron conditions. We studied the role of the bacteriophage beta genome in this apparent regulation of toxin production by iron. Using a passive immune hemolysis assay to detect toxin antigen production in individual plaques, we identified rare phage mutants that were toxinogenic in high-iron medium. Lysogenic derivatives of C. diphtheriae C7 harboring such phage mutants were constructed. The lysogens were compared with wild-type strain C7(beta) for their ability to produce toxin in deferrated liquid medium containing varying amounts of added iron. Quantitative tests for extracellular toxin were performed by competitive-binding radioimmunoassays. We identified phenotypically distinct mutant strains that produced slightly, moderately, or greatly increased yields of toxin antigen under high-iron conditions. The toxin produced by the mutant lysogens was biologically active and immunochemically indistinguishable from wild-type toxin. Complementation experiments demonstrated that the phage mutation designated tox-201 had a cis-dominant effect on the expression of the toxin structural gene of phage beta. The characteristics of the tox-201 mutation suggest that it defines a regulatory locus of phage beta that is involved in control of toxinogenesis by iron in C. diphtheriae.
mesh_terms: D001435:Bacteriophages / Q000235:genetics*; D003353:Corynebacterium diphtheriae / Q000378:metabolism*; D004167:Diphtheria Toxin / Q000096:biosynthesis* / Q000235:genetics; D005296:Ferrous Compounds / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D005814:Genes, Viral; D007501:Iron / Q000494:pharmacology*; D008242:Lysogeny; D009154:Mutation
chemical_list: D004167:Diphtheria Toxin; D005296:Ferrous Compounds; D007501:Iron